Semiquantitative Human Papillomavirus Type 16 Viral Load and the Prospective Risk of Cervical Precancer and Cancer

Abstract

We examined whether higher human papillomavirus type 16 (HPV16) viral load predicted risk of cervical intraepithelial neoplasia 3 (CIN3) or cancer (together termed z zCIN3) within a cohort of 20,810 women followed for 10 years with cytologic screening. Semiquantitative viral load for HPV16 was measured on baseline cervicovaginal specimens using a type-specific hybridization probe test with signal amplification. An increased risk of z zCIN3 associated with higher HPV16 viral load was found only among cytologically negative women in early follow-up, suggesting that these cases were related to the detection of prevalent lesions missed at baseline. Women with higher HPV16 viral load were more likely to undergo ablative treatment during follow-up than those with lower viral load (P trend = 0.008), possibly diminishing any additional risk for z zCIN3 attributable to higher HPV16 viral loads.

Determination of viral load thresholds in cervical scrapings to rule out CIN 3 in HPV 16, 18, 31 and 33‐positive women with normal cytology

“…Still, this group may include a small proportion of women with prevalent high-grade CIN lesions missed by cytology. Since we anticipate that such cases would display increased viral copy numbers that fall in the higher viral load percentiles, 19 we consider the sensitivity of the 33rd percentile thresholds set in this study not over represented. It is also noteworthy that total DNA can be derived from many types of cells from the cervix, including inflammatory cells that are not HPV host cells.…”

“…6,7,11,13,18 Nevertheless, also amongst HPV 16 positive women with normal cytology defined by hc2, semiquantitative viral load assessment could better predict those women who are more likely to have prevalent CIN 3 lesions. 19 Still, most studies had in common a substantial overlap of viral load values amongst women with and without high-grade CIN, especially in the range of high viral loads. This precludes setting a cut-off value for high-grade CIN on the basis of high viral loads.…”

“…6 In this context, it has been demonstrated for HPV 16 infections that increased viral loads would be associated with an increased risk of CIN 2 whereas reduced amounts of viral DNA reflects the absence of CIN lesions or viral clearance, which is associated with regression of CIN lesions. 7 Still, data in favor of viral load being informative for risk of CIN 2 are mainly based on HPV 16, whereas those of hrHPV types other than HPV 16 are limited and inconsistent, [8][9][10][11][12][13][14][15][16][17][18][19] obviously because of the generally low numbers of women with non-HPV 16 types studied so far. Moreover, the potential value of viral load assessment is quite likely to be dependent on the method used to define HPV positivity since its impact seems lower when the hybridization-based hybrid capture 2 (hc2) is used to define HPV positivity when compared with PCR-based assays, which generally display a higher analytical sensitivity.…”

“…POBASCAM; 18,19) and of a group of women with underlying histologically confirmed CIN. In this way, we succeeded in setting viral load threshold levels for these 4 hrHPV types below which underlying CIN 3 could be excluded.…”

Cross‐sectional analysis of oncogenic HPV viral load and cervical intraepithelial neoplasia

“…As a result, several groups have suggested that viral load may be used as a predictor of cervical lesion clearance. 12,16,18,30 A word of caution should be taken, however, since high viral load values with normal cytology may represent equivocal diagnosis of cervical lesions, 23 and further research is needed.…”